Lung Cancer
Conditions
Keywords
adenocarcinoma of the lung, squamous cell lung cancer, large cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. Giving carboplatin and gemcitabine together with thalidomide before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving carboplatin and gemcitabine together with thalidomide works in treating patients who are undergoing surgery for stage II or stage III non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * Determine the complete and partial response rates in patients with stage II or IIIA non-small cell lung cancer treated with neoadjuvant carboplatin, gemcitabine hydrochloride, and thalidomide. Secondary * Determine, preliminarily, the mechanism of action and activity of thalidomide against lung cancer. * Determine the 1-year and 2-year survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Determine the operative mortality of patients treated with this regimen. OUTLINE: This is a pilot study. Patients receive carboplatin intravenously (IV) over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and oral thalidomide once daily on days 1-21. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks after the completion of chemotherapy, patients with resectable tumors undergo surgical resection. After completion of study treatment, patients are followed every 3 months for 2 years.
Interventions
DRUGcarboplatin
Day 1 of Cycles 1, 2 and 3 - intravenously (IV) 30 minutes (Area Under the Curve = 5.5)
DRUGgemcitabine hydrochloride
Days 1 and 8 of Cycles 1, 2 and 3 - 30 minute IV, 1000 mg/m2.
DRUGthalidomide
Oral administration: Cycle 1 - Day 1 50 mg, Day 2 100 mg, Day 3 150 mg, Day 4 and continuing until end of study treatment 200 mg.
PROCEDUREconventional surgery
Resection - between 2 and 6 weeks following last dose of chemotherapy.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following histologic subtypes: * Squamous cell carcinoma * Adenocarcinoma * Large cell undifferentiated carcinoma * Stage II or IIIA disease * Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral Computerized Axial Tomography (CT) scan * No tumor involving the superior sulcus (e.g., Pancoast tumor) * Karnofsky performance status 70-100% * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Creatinine ≤ 2 mg/dL * Bilirubin \< 2 mg/dL * Aspartate aminotransferase (AST) \< 3 times upper limit of normal
Exclusion criteria
* Pregnant or nursing * No nursing during and for ≥ 4 weeks after completion of study treatment * Positive pregnancy test * Fertile female patients must use 2 effective methods of contraception 4 weeks before, during, and for 4 weeks after completion of study treatment * Fertile male patients must use effective barrier contraception during and for 4 weeks after completion of study treatment * Blood, sperm, or ova donation during study treatment * Post obstructive pneumonia * Other serious infection or medical illness that would preclude study participation * Other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other malignancy that is unlikely to affect survival for the next 3 years * Less than 5 years since prior resection of lung disease * Prior systemic chemotherapy or radiotherapy for non-small cell lung cancer (NSCLC) * Other concurrent chemotherapy or radiotherapy * Concurrent hormonal therapy or immunotherapy * Other concurrent anticancer therapy * Other concurrent investigational agents * Concurrent participation in another clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Reporting Clinical Response | At end of 3 -21 day cycles of treatment | Objective clinical response measuring using tumor assessments: Complete Response (CR) = disappearance of all target and non-target lesions and normalization of tumor marker level, if applicable. Pathological Complete Response (PCR) = No viable tumor cells in specimen determined by light microscopy. Partial Response (PR) = at least 30% decrease in the sum of longest diameter of target lesions from baseline. Progressive Disease (PD) = at least 20% increase in the sum of longest diameters of target lesions from baseline or new lesions. Stable Disease (SD) = Neither PR or PD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Alive at 56 Months (End of Study) | Up to 56 months | Patients alive from date of enrollment to date of death or censored at date of last contact (Overall Survival). |
| Number of Patients Disease-free at 1 Year | 1 year | Calculated from date of enrollment to date of recurrence or death, whichever came first |
| Number of Patients Disease-free at 2 Years | 2 Years | Calculated from date of enrollment to date of recurrence or death, whichever came first |
| Number of Patients Alive at 1 Year (Survival) | 12 Months | Participants who were alive at one year from date of enrollment . |
| Number of Patients Alive at 2 Years (Survival) | 24 Months | Participants who were alive at 2 years from date of enrollment. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from 3 participating study centers.
Participants by arm
| Arm | Count |
|---|---|
| Intent-to-Treat Patients receiving at least one dose of each study drug (carboplatin, gemcitabine and thalidomide). | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Intent-to-Treat |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 53 years |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 1 / 19 |
Outcome results
Primary
Number of Patients Reporting Clinical Response
Objective clinical response measuring using tumor assessments: Complete Response (CR) = disappearance of all target and non-target lesions and normalization of tumor marker level, if applicable. Pathological Complete Response (PCR) = No viable tumor cells in specimen determined by light microscopy. Partial Response (PR) = at least 30% decrease in the sum of longest diameter of target lesions from baseline. Progressive Disease (PD) = at least 20% increase in the sum of longest diameters of target lesions from baseline or new lesions. Stable Disease (SD) = Neither PR or PD.
Time frame: At end of 3 -21 day cycles of treatment
Population: 2 of 22 patients did not receive all 3 drugs for all 3 cycles - only 20 patients achieved this and are thereby included here in the evaluable population analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evaluable Patients | Number of Patients Reporting Clinical Response | Complete Response | 0 Participants |
| Evaluable Patients | Number of Patients Reporting Clinical Response | Pathological Complete Response | 0 Participants |
| Evaluable Patients | Number of Patients Reporting Clinical Response | Partial Response | 14 Participants |
| Evaluable Patients | Number of Patients Reporting Clinical Response | Stable Disease | 4 Participants |
| Evaluable Patients | Number of Patients Reporting Clinical Response | Progressive Disease | 2 Participants |
Secondary
Number of Patients Alive at 1 Year (Survival)
Participants who were alive at one year from date of enrollment .
Time frame: 12 Months
Population: Calculated from date of first date of enrollment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evaluable Patients | Number of Patients Alive at 1 Year (Survival) | 21 Participants |
Secondary
Number of Patients Alive at 2 Years (Survival)
Participants who were alive at 2 years from date of enrollment.
Time frame: 24 Months
Population: Calculated from date of first date of enrollment to date of death.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evaluable Patients | Number of Patients Alive at 2 Years (Survival) | 16 Participants |
Secondary
Number of Patients Alive at 56 Months (End of Study)
Patients alive from date of enrollment to date of death or censored at date of last contact (Overall Survival).
Time frame: Up to 56 months
Population: Calculated from study entry date to date of death or censored at date of last contact.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evaluable Patients | Number of Patients Alive at 56 Months (End of Study) | 8 Participants |
Secondary
Number of Patients Disease-free at 1 Year
Calculated from date of enrollment to date of recurrence or death, whichever came first
Time frame: 1 year
Population: Calculated from study entry date to date of recurrence or date of death, whichever came first.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evaluable Patients | Number of Patients Disease-free at 1 Year | 14 Participants |
Secondary
Number of Patients Disease-free at 2 Years
Calculated from date of enrollment to date of recurrence or death, whichever came first
Time frame: 2 Years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evaluable Patients | Number of Patients Disease-free at 2 Years | 8 Participants |